Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, PR China.
Hum Exp Toxicol. 2011 Aug;30(8):920-9. doi: 10.1177/0960327110384286. Epub 2010 Sep 27.
Cadmium (Cd) is the major component of polluted environment, which has numerous undesirable effects on health. Cd could induce apoptosis of HEK293 cells, and the mitochondria may play a key role. However, the mode of action is unclear. In the present study, we aimed to evaluate the ability of the Cd to induce dysfunction of mitochondria. We examined the effect of cadmium chloride (1, 5 and 10 μM) on mitochondrial membrane permeability and potential as well as oxidative stress markers in mitochondria isolated from HEK293 cells. We found that Cd could directly increase in permeability and decrease in membrane potential of mitochondria, even resulted in mitochondrial swelling, and that Cd could inhibit the activities of ATPase, lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), enhanced the levels of reactive oxygen species (ROS) and lipid peroxidation (LPO). On the whole, the results show that Cd can directly lead to mitochondrial dysfunction of HEK293 cells, including increased permeability, inhibiting respiration and evoking oxidative stress. Thus, for the first time, this paper makes an overall analysis of Cd-induced changes of structure and function of isolated mitochondria. Our findings may also have general implications in Cd-induced apoptosis by mitochondria pathway.
镉 (Cd) 是污染环境的主要成分，对健康有许多不良影响。Cd 可诱导 HEK293 细胞凋亡，线粒体可能发挥关键作用。然而，其作用方式尚不清楚。本研究旨在评估 Cd 诱导线粒体功能障碍的能力。我们检测了氯化镉 (1、5 和 10 μM) 对 HEK293 细胞线粒体分离物中线粒体膜通透性和电位以及氧化应激标志物的影响。结果发现 Cd 可直接增加线粒体通透性，降低膜电位，导致线粒体肿胀，抑制 ATP 酶、乳酸脱氢酶 (LDH)、超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-Px) 的活性，增加活性氧 (ROS) 和脂质过氧化 (LPO) 的水平。总的来说，这些结果表明 Cd 可直接导致 HEK293 细胞线粒体功能障碍，包括通透性增加、抑制呼吸和引发氧化应激。因此，本文首次对 Cd 诱导的分离线粒体结构和功能变化进行了全面分析。我们的研究结果也可能对线粒体途径诱导的 Cd 诱导细胞凋亡具有普遍意义。
